Our principle objective is to determine how the adhesive properties of cancer cells, mediated through Activated Leukocyte Cellular Adhesion Molecule (ALCAM), contribute to tumor cell metastasis. The goal is to propagate this understanding to establish improved diagnostics and treatment strategies for metastatic cancer. This research project will be part of a training mechanism that will provide instruction for Ms. Jones-Paris in basic research and clinical evaluation of the cancer and to translate the functional role and regulation of ALCAM into clinical significance in the realm of cancer progression. Specific Aims: ALCAM regulates the adhesion and migration of the tumor cells by engaging in ALCAM- ALCAM interactions at cell-cell junctions. The aims of this proposal include 1) identify the mechanisms regulating ALCAM in invasive cancer, and 2) define the clinical value of ALCAM as an indicator for the progression and/or treatment response of tumor-induced bone disease in cancer. Health relatedness (impact): Metastatic dissemination away from the primary tumor is the main cause of cancer related deaths. Improved monitoring of disease progression and treatment response will diminish loss of life and increase the quality of life for patients wit metastatic disease and secondary complications. Training program design: The training program has incorporated the resources, collaborations, and experimental guidance to prepare Celeste for her career goals and to achieve the proposed research. Celeste is enrolled in the Cellular and Molecular Pathology program and is directly trained in the Zijlstra laboratory. Clinical and research expertise will be obtained collaboratively through Vanderbilt's Breast Cancer SPORE, Department of Urologic Surgery, Center for Bone Biology, and Human Tissue Acquisition Core. Methods for achieving stated goals: The contribution of ALCAM to cancer progression and metastasis will be determined by altering the level or molecular composition of ALCAM expressed in metastatic cancer cell lines and monitoring the consequences for in vitro and in vivo cell behavior. The clinical value of ALCAM will be determined in preclinical mouse models of metastatic cancer. Human serum from longitudinal clinical trials will be used to determine if a correlation with human disease progression and treatment response exists. Accomplishing the stated academic goals will include completion of the included course work and successful conclusions of the qualifying examinations. This proposal will contribute in part of these examinations. Collaborative engagement of the Breast Cancer SPORE, Department of Urologic Surgery, and the Center for Bone Biology will ensure proper training in cancer. In addition, the recruitment of both clinical as well as basic science mentors allows for a comprehensive perspective in the training program. PUBLIC HEALTH RELEVANCE: Diagnosing cancer patients and monitoring their response to therapy is a key challenge in cancer treatment. We propose that the detection of the cell-cell adhesion molecule ALCAM produced by the tumor will advance our understanding of tumor dissemination mechanisms, make it possible to monitor disease progression and possibly predict disease recurrence in cancer patients.